1. Field of the Invention
The present invention relates to a technology of enhancing radiosensitivity using microRNA, more particularly to a radiosensitizer composition comprising at least one selected from the group consisting of microRNA-26b, microRNA-203 and microRNA-200c, an anticancer supplement, and a method for enhancing radiosensitivity of cancer cells using the same.
2. Description of the Related Art
Cancer therapy may be largely classified into surgery, radiotherapy, and chemotherapy. Among them, radiotherapy is currently known as an essential treatment method in various kinds of cancer, but several problems have been pointed out, including radioresistance acquisition of cancer cells, decrease in radiotherapy effect due to normal tissue damage by high dose radiotherapy, and the like. Thus, many studies are conducted on radiosensitizer for enhancing the effect of radiotherapy.
As radiosensitizer reported to date, anticancer drugs such as taxol or cysplatin are known, but they have limitations in practical use because toxicity of anticancer drugs may be exhibited complicatedly with side effects of radiotherapy including inflammation at the site of radiotherapy, gastrointestinal disorder, nausea, vomiting, and the like, when combined with radiotherapy. And, as radiotherapy enhancer that is used only for radiotherapy without properties as anticancer drugs, tirapazamine is known, but it has effect only on tumor cells with hypoxia, and is known to have an insignificant effect in clinical radiotherapy because drug delivery into tumor tissue is insufficient due to internal pressure of tumor, which is intrinsic to hypoxia. In addition, although there have been many attempts to develop drugs for increasing radiotherapy effect, only extremely few drugs may be used in practical patient treatment, and unexpected resistance problem is being raised in a part of the existing successful drugs. Thus, there is demand for development of a radiosensitizing method specifically acting on cancer cells.
Particularly, in the treatment of brain tumor, radiotherapy is important as well as surgery and anticancer therapy. Since brain tumor such as malignant glioma (GBM) has properties of high proliferation rate, hypoxia, angiogenesis, brain infiltration, and high cancer recurrence rate, there is a limitation with chemotherapy. Although radiotherapy may induce cell cycle delay or cell death through DNA damage in the cells by radiation to remove abnormal cells, due to intrinsic radioresistance of cancer cells and resistance increase according to radiotherapy, radioresistant cancer cells may induce cancer recurrence and they may also become resistant to anticancer drugs. Thus, there is urgent need for development of radiosensitivity enhancer that may enhance radiosensitivity of cancer cells with intrinsic radioresistance, minimize side effect, and optimize radiotherapy effect through delay in the repair of DNA damage induced by radiation in the cells.
Meanwhile, microRNA (or miRNA) refers to nonprotein-coding RNA that controls expression of various genes, and it inhibits translation of mRNA, or post-transcriptionally inhibits gene expression by inducing decomposition of mRNA. The post-transcriptional regulation is used as a strong regulation method in the process requiring exact and detailed gene expression such as intracellular signal transfer, and since about half of gene expression changes due to external stimulation are post-transcriptionally regulated, the post-transcriptional regulation is reported to play a very important function in the regulation of total gene expression. It was found through several studies that microRNA plays an important function of regulating many biological processes such as cell differentiation, proliferation, cell death, cytogenesis, immune, metabolism and stem cell maintenance, and the like. It was also found that several microRNAs function as tumor inducer or tumor inhibitor.
As the results of studies on correlationship between expression levels of microRNA-7, microRNA-26b, microRNA-203 and microRNA-200c and radioresistance in brain tumor cell, glioma cells, the inventors found out that the microRNAs may effectively increase radiosensitivity of cancer cells through delay in the repair of DNA damage by radiation. Thus, the present invention is based on the discovery that these microRNAs may enhance radiosensitivity of cancer cells having intrinsic radioresistance to maximize radiotherapy effect, and they may be also applied for an anticancer supplement.